A number of studies indicate that a point mutation at either position 12, 13, 59 or 61 or ras p21 proteins is associated with a fundamental change in their biochemical properties including their ability to transform cells. The main objective of this project is to study the conformational differences between non-transforming and transforming ras p21 proteins as well as the conformational changes upon addition of GTP. Results obtained so far are as follows: (1) Both glycine-containing (Gly-peptide) and valine-containing (Val-peptide) 34 amino acid residue peptides of N-terminal segments of p21 proteins have been synthesized and purified. Their structures were confirmed by mass spectroscopy and peptide sequencing. (2) It is notable that a single amino acid substitution in the N-terminal segment produces a distinct change in the solubility properties. (3) In Tris buffer (pH 7.4), the Gly-peptide adopted a largely beta-sheet structure. However, in 40% trifluoroethanol (TFE), the Gly-peptide showed an increased amount of alpha-helical structure (46%). (4) The Val-peptide in ammonium acetate buffer (pH 7.4) adopted a greater amount of alpha-helical structure relative to that of the Gly-peptide in Tris buffer. (5) The addition of GTP to the Gly-peptide induces a larger amount of change in its conformation. In contrast, upon addition of nucleotides to the Val-peptide solution, little overall conformational change was noted. (6) When the Gly-peptide was added to the solution containing GTP and SDS, the line widths of all three P-31 NMR signals, alpha, beta, and gamma, were broadened (10 Hz for beta and gamma, and 5 Hz for alpha). The result implies that there is a complex formation between GTP and the Gly-peptide. (7) Equilibrium dialysis experiments indicate that the binding strength of the Gly-peptide and Val-peptide with GTP are comparable to those of intact p21 proteins. The model peptides bind GTP and ATP indiscriminately. (8) N-Terminal segments of p21 proteins are involved in the hydrolysis of GTP.